DNA is a contaminant of process solutions and a potential contaminant of purified biotechnology products including therapeutic proteins and vaccines. Regulatory agencies worldwide specify low DNA levels to ensure adequate patient safety. It has also become apparent that contaminating DNA is an impediment to the efficiency of bioprocessing operations, including filtration and purification. It has been suggested recently that DNA may also be responsible for the formation of product aggregates (Gagnon, 2010, Bioprocessing Journal, 9(2) 14-24). Aggregates severely complicate purification and, if not removed, can threaten the safety of patients receiving therapy.
Current methods for DNA reduction focus on anion exchange materials and variants thereof, where DNA is bound by its negative charges to the positively charged anion exchanger. However this method has no utility when the DNA exists in a process solution containing a product that also binds to anion exchangers because the product is removed along with the DNA. Anion exchange-based removal methods are also precluded from application with live cell cultures because anion exchange resins bind cells. A variant of this approach involves DNA removal with hydroxyatite, but this approach has the same limitations as anion exchange. Alternatively, DNA levels may be reduced by the application of nuclease enzymes such as benzonase. However, nuclease-based methods can suffer from high expense. Indeed, small DNA fragments are in some cases more difficult to remove than relatively intact DNA. Nuclease enzymes are also incompatible with live cultures.